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| ID | Type | Description | Link |
|---|---|---|---|
| COL MIG-106 | Other Identifier | CoLucid Pharmaceuticals | |
| H8H-CD-LAHG | Other Identifier | Eli Lilly and Company |
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| Name | Class |
|---|---|
| Algorithme Pharma Inc | INDUSTRY |
| Cognitive Research Corporation | INDUSTRY |
| CoLucid Pharmaceuticals | INDUSTRY |
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This will be a randomized, single dose, double-blind, placebo-controlled, Latin-square design with 5-period (full) crossover study with participants randomized to treatment sequences. Participants will complete all 5 Periods.
During each Period, participants will come to the clinical research unit (CRU) and remain overnight before being dosed with a single dose of either lasmiditan, alprazolam, or placebo in the morning. Cognitive testing and driving simulation will be conducted post dosing. Participants will have a washout of at least 5 days between each Period.
This study is designed to test non-inferiority of lasmiditan doses relative to placebo, with an alprazolam test versus placebo to confirm the sensitivity of the simulator to detect treatment effects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lasmiditan 50mg (milligrams) | Experimental | Participants received 50mg of Lasmiditan tablets given as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. |
|
| Lasmiditan 100mg | Experimental | Participants received 100mg of Lasmiditan tablets given as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. |
|
| Lasmiditan 200mg | Experimental | Participants received 200mg of Lasmiditan tablets given as single doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. |
|
| Alprazolam 1mg | Active Comparator | Participants received 1mg of Alprazolam tablets as single oral dose on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. |
|
| Placebo | Placebo Comparator | Participants received placebo tablets identical to Lasmiditan, administered as single oral dose on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lasmiditan | Drug | Dose is based on treatment sequence in 5-way crossover |
|
| Measure | Description | Time Frame |
|---|---|---|
| Simulated Driving Performance in Healthy Participants as Measured by Standard Deviation of Lateral Position (SDLP) Using the Cognitive Research Corporation Driving Simulator-MiniSim (CRCDS-MiniSim) | The standard deviation of lateral position (SDLP) is the primary parameter used as stable measure of driving performance with high test-retest reliability. It measures the driver's ability to stay in a constant position within the driving lane. Variations in the lateral position are recorded and analyzed. SDLP, was analyzed using a mixed model with fixed effects for sequence, period, and treatment, and a random effect for participant within sequence. A variance component covariance structure and Kenward-Roger degrees of freedom was used. | Approximately 90 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
| Measure | Description | Time Frame |
|---|---|---|
| Karolinska Sleepiness Scale (KSS) Score | The KSS is used to assess subjective level of sleepiness. This is a participant self-report measure of situational sleepiness and provides an assessment of alertness/sleepiness at a particular point in time. It is a 9-point categorical Likert scale on which the participant rates sleepiness from 1 (very alert) to 9 (very sleepy/fighting sleep), with higher scores indicating more sleepiness and lower scores indicating more alertness. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Data presented are the number of participants who experienced 1 or more AEs (all causalities and drug-related) and serious AEs (SAEs). A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this record. | Up To 35 days |
Inclusion Criteria:
Exclusion Criteria:
History or presence of clinically significant condition that, in the opinion of the Investigator, would jeopardize the safety of the participant or the validity of the study results.
A history within 2 years of, or current treatment for, a sleeping disorder (including excessive snoring, obstructive sleep apnea), or a chronic painful condition that interferes with the participant's sleep.
A history of difficulty either falling asleep or staying asleep in the previous 3 months, that is considered clinically significant by the investigator.
Participant has a history or diagnosis of any of the following conditions:
Expected to use any other medication or dietary supplement to promote sleep including over- the-counter sleep medications, during their participation in the study.
Participant consumes excessive amounts of coffee, tea, cola, or other caffeinated beverages per day.
Participant has traveled across 1 or more time zones (transmeridian travel) in the last 2 weeks prior to randomization or is expected to travel across 1 or more time zones during the study.
Expected to work on a rotating shift during their participation in the study.
Participant works a night shift.
History or presence of seizure disorder.
History of urinary retention, angle closure glaucoma, or increased ocular pressure.
History of gastrointestinal tract surgery, except for appendectomy.
Has abnormal finding on the physical exam, medical history, electrocardiogram (ECG), or clinical laboratory results at Screening, that are considered clinically significant by the investigator.
Presence of out-of-range cardiac interval on the screening ECG or other clinically significant ECG abnormalities
History of orthostatic hypotension, fainting spells, or blackouts, that are considered clinically significant by the investigator.
The presence of chronic or acute infections, that are considered clinically significant by the investigator.
History of allergy/hypersensitivity (including drug allergies) that are deemed relevant to the study as judged by the Investigator.
Use of psychoactive prescription or non-prescription medications, psychoactive nutritional supplements or herbal preparations within 2 weeks or 5 half-lives (whichever is longer) of admission to the clinical research unit (CRU) on Day -1.
Has received any previous study drug within 30 days prior to the first dose of this study drug.
Is a smoker of more than 10 cigarettes or eCigarettes, or 3 cigars or 3 pipes per day, and is unable to refrain from smoking while confined to the CRU.
Has any history of dependency or treatment for substance abuse within the past 2 years.
Participant with a history of alcoholism or who consumes excessive amounts of alcohol.
Participants who consume alcohol on a regular basis (i.e., ≥ 5 times/week) before bedtime will be excluded from the study.
Inability to comply with the dietary regimen of the clinical research center.
Pregnancy / positive pregnancy test.
Planning to become pregnant during the study or within 1 month of study completion.
Inability to use adequate contraception during the study. It is recommended that adequate contraception be used for 30 days following completion of the study.
Has a positive screen for alcohol or other drugs of abuse (amphetamines, methamphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates).
Has a history for Hepatitis B, Hepatitis C , or Human Immunodeficiency Virus (HIV) at Screening or has been previously treated for Hepatitis B, Hepatitis C, or HIV.
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Algorithme Pharma | Mount Royal | Quebec | H3P3P1 | Canada |
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Crossover study with five study periods, each participant received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and Placebo as per the dosing sequence in each period. The washout period between dosing in consecutive study periods was at least 7 days.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Lasmiditan 50 mg, Period 2: Lasmiditan 100 mg, Period 3: Placebo, Period 4: Lasmiditan 200 mg and Period 5: Alprazolam 1 mg |
| FG001 | Sequence 2 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Lasmiditan 100 mg, Period 2: Lasmiditan 200 mg, Period 3: Lasmiditan 50 mg, Period 4: Alprazolam 1 mg and Period 5: Placebo |
| FG002 | Sequence 3 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Lasmiditan 200 mg, Period 2: Alprazolam 1 mg, Period 3: Lasmiditan 100 mg, Period 4: Placebo and Period 5: Lasmiditan 50 mg |
| FG003 | Sequence 4 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Alprazolam 1 mg, Period 2: Placebo, Period 3: Lasmiditan 200 mg, Period 4: Lasmiditan 50 mg and Period 5: Lasmiditan 100 mg |
| FG004 | Sequence 5 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Placebo, Period 2: Lasmiditan 50 mg, Period 3: Alprazolam 1 mg, Period 4: Lasmiditan 100 mg and Period 5: Lasmiditan 200 mg |
| FG005 | Sequence 6 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Alprazolam 1 mg, Period 2: Lasmiditan 200 mg, Period 3: Placebo, Period 4: Lasmiditan 100 mg and Period 5: Lasmiditan 50 mg |
| FG006 | Sequence 7 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Placebo, Period 2: Alprazolam 1 mg, Period 3: Lasmiditan 50 mg, Period 4: Lasmiditan 200 mg and Period 5: Lasmiditan 100 mg |
| FG007 | Sequence 8 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Lasmiditan 50 mg, Period 2: Placebo, Period 3: Lasmiditan 100 mg, Period 4: Alprazolam 1 mg and Period 5: Lasmiditan 200 mg |
| FG008 | Sequence 9 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Lasmiditan 100 mg, Period 2: Lasmiditan 50 mg, Period 3: Lasmiditan 200 mg, Period 4: Placebo and Period 5: Alprazolam 1 mg |
| FG009 | Sequence 10 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Lasmiditan 200 mg, Period 2: Lasmiditan 100 mg, Period 3: Alprazolam 1 mg, Period 4: Lasmiditan 50 mg and Period 5: Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
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| Period 2 |
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| Period 3 |
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| Period 4 |
| |||||||||||||||||||
| Period 5 |
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All randomized participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Sequence 1 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Lasmiditan 50 mg, Period 2: Lasmiditan 100 mg, Period 3: Placebo, Period 4: Lasmiditan 200 mg and Period 5: Alprazolam 1 mg |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Simulated Driving Performance in Healthy Participants as Measured by Standard Deviation of Lateral Position (SDLP) Using the Cognitive Research Corporation Driving Simulator-MiniSim (CRCDS-MiniSim) | The standard deviation of lateral position (SDLP) is the primary parameter used as stable measure of driving performance with high test-retest reliability. It measures the driver's ability to stay in a constant position within the driving lane. Variations in the lateral position are recorded and analyzed. SDLP, was analyzed using a mixed model with fixed effects for sequence, period, and treatment, and a random effect for participant within sequence. A variance component covariance structure and Kenward-Roger degrees of freedom was used. | All randomized participants who received study drug and have evaluable data for simulated driving performance. | Posted | Mean | Standard Deviation | Centimeters (cm) | Approximately 90 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
|
Up To 35 days
All randomized participants who received study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received placebo tablets identical to Lasmiditan, administered as single oral dose on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cerebellar haematoma | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 | ClinicalTrials.gov@lilly.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 23, 2017 | Feb 4, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Dec 6, 2016 | Feb 4, 2019 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D008881 | Migraine Disorders |
| ID | Term |
|---|---|
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C554777 | lasmiditan |
| D000525 | Alprazolam |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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|
|
| Alprazolam | Drug | Active comparator based on treatment sequence in 5-way crossover |
|
| Placebo | Other | Placebo comparator based on treatment sequence in 5-way crossover |
|
| Approximately 85 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
| Percentage of Participants With Self-Reported Readiness to Drive | On each dosing day participants were asked "Right now do you feel safe to drive?". Pair-wise comparisons for readiness to drive were analyzed using McNemar test. | Approximately 85 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
| Motivational and Self-Appraisal Visual Analog Scale (VAS) | After completing the driving simulation, participants assessed their own performance and their level of motivation to perform at their best during the driving simulation. Participants responded to 2 questions: 1. How well do you think you drove for the last 60 minutes? 2. How motivated did you feel to drive at your best during the last 60 minutes of driving?. Participants recorded their response to each question by writing a vertical line on a 100 millimeters (mm) horizontal, linear visual analog scale indicating their level of performance (Not Satisfactory to Satisfactory) and motivation (Not Motivated to Motivated). Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. Scores ranged from 0-100 mm, with higher scores indicating motivated and satisfactory and lower scores indicating not motivated and not satisfactory. | Approximately 2.5 hours post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
| Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test | The SDC Test, a digit symbol substitution test that is sensitive to changes in information processing speed, provides measures of response speed and accuracy. The test was administered prior to the simulated driving sessions. The principal test score measures the number of correct responses in 120 seconds. SDC was used in this study to measure attention, visual scanning, working memory, and speed of information processing. Scores range from 0 (No correct responses). A higher score indicates greater processing speed. | Approximately 85 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
| Driving Performance Using the CRCDS-MiniSim - Lane Exceedance | The CRCDS-MiniSim is a PC-based research driving simulator that provides a realistic automotive driving environment. The present study employs the Country Vigilance-Divided Attention (CVDA) driving scenario, a 62.1 mile (100 km), monotonous, two lane highway driving task that includes a secondary visual vigilance task (DA). The monotonous Country Vigilance scenario has been demonstrated to be sensitive to detect the effects of fatigue or sleepiness on driving performance. Lane exceedance is the number of lane exceedances, an indication of lane position control, (i.e., the driver's ability to stay within his/her lane), as measured by the number of times that the front left or right tire of the vehicle crosses over the right or left lane boundary. | Approximately 90 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
| Driving Performance Using the CRCDS-MiniSim - Speed Deviation | The CRCDS-MiniSim is a PC-based research driving simulator that provides a realistic automotive driving environment. The present study employs the Country Vigilance-Divided Attention (CVDA) driving scenario, a 62.1 mile (100 km), monotonous, two lane highway driving task that includes a secondary visual vigilance task (DA). The monotonous Country Vigilance scenario has been demonstrated to be sensitive to detect the effects of fatigue or sleepiness on driving performance. Speed deviation is a measure of intra-individual variability. Measures that assess an individual's failure to maintain consistent performance are more sensitive to sedation than are measures of absolute performance. | Approximately 90 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
| Sequence 2 |
Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Lasmiditan 100 mg, Period 2: Lasmiditan 200 mg, Period 3: Lasmiditan 50 mg, Period 4: Alprazolam 1 mg and Period 5: Placebo |
| BG002 | Sequence 3 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Lasmiditan 200 mg, Period 2: Alprazolam 1 mg, Period 3: Lasmiditan 100 mg, Period 4: Placebo and Period 5: Lasmiditan 50 mg |
| BG003 | Sequence 4 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Alprazolam 1 mg, Period 2: Placebo, Period 3: Lasmiditan 200 mg, Period 4: Lasmiditan 50 mg and Period 5: Lasmiditan 100 mg |
| BG004 | Sequence 5 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Placebo, Period 2: Lasmiditan 50 mg, Period 3: Alprazolam 1 mg, Period 4: Lasmiditan 100 mg and Period 5: Lasmiditan 200 mg |
| BG005 | Sequence 6 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Alprazolam 1 mg, Period 2: Lasmiditan 200 mg, Period 3: Placebo, Period 4: Lasmiditan 100 mg and Period 5: Lasmiditan 50 mg |
| BG006 | Sequence 7 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Placebo, Period 2: Alprazolam 1 mg, Period 3: Lasmiditan 50 mg, Period 4: Lasmiditan 200 mg and Period 5: Lasmiditan 100 mg |
| BG007 | Sequence 8 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Lasmiditan 50 mg, Period 2: Placebo, Period 3: Lasmiditan 100 mg, Period 4: Alprazolam 1 mg and Period 5: Lasmiditan 200 mg |
| BG008 | Sequence 9 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Lasmiditan 100 mg, Period 2: Lasmiditan 50 mg, Period 3: Lasmiditan 200 mg, Period 4: Placebo and Period 5: Alprazolam 1 mg |
| BG009 | Sequence 10 | Participants received Lasmiditan (50 milligrams (mg), 100mg, and 200mg), Alprazolam 1mg and placebo as per the below dosing schedule. Period 1: Lasmiditan 200 mg, Period 2: Lasmiditan 100 mg, Period 3: Alprazolam 1 mg, Period 4: Lasmiditan 50 mg and Period 5: Placebo |
| BG010 | Total | Total of all reporting groups |
| Participants |
| No |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
|
| Region of Enrollment | Count of Participants | Participants | No |
|
| Placebo |
Participants received placebo tablets identical to Lasmiditan, administered as single oral dose on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. |
| OG001 | Lasmiditan 50mg | Participants received 50mg of Lasmiditan tablets given as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. |
| OG002 | Lasmiditan 100mg | Participants received 100mg of Lasmiditan tablets given as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. |
| OG003 | Lasmiditan 200mg | Participants received 200mg of Lasmiditan tablets given as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. |
| OG004 | Alprazolam 1mg | Participants received 1mg of Alprazolam tablets as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. |
|
|
|
| Secondary | Karolinska Sleepiness Scale (KSS) Score | The KSS is used to assess subjective level of sleepiness. This is a participant self-report measure of situational sleepiness and provides an assessment of alertness/sleepiness at a particular point in time. It is a 9-point categorical Likert scale on which the participant rates sleepiness from 1 (very alert) to 9 (very sleepy/fighting sleep), with higher scores indicating more sleepiness and lower scores indicating more alertness. | All randomized participants who received study drug and have evaluable data for karolinska sleepiness scale. | Posted | Mean | Standard Deviation | Units on a scale | Approximately 85 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
|
|
|
|
| Secondary | Percentage of Participants With Self-Reported Readiness to Drive | On each dosing day participants were asked "Right now do you feel safe to drive?". Pair-wise comparisons for readiness to drive were analyzed using McNemar test. | All randomized participants who received study drug and have evaluable data for self-reported readiness to drive. | Posted | Number | Percentage of Participants | Approximately 85 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
|
|
|
| Secondary | Motivational and Self-Appraisal Visual Analog Scale (VAS) | After completing the driving simulation, participants assessed their own performance and their level of motivation to perform at their best during the driving simulation. Participants responded to 2 questions: 1. How well do you think you drove for the last 60 minutes? 2. How motivated did you feel to drive at your best during the last 60 minutes of driving?. Participants recorded their response to each question by writing a vertical line on a 100 millimeters (mm) horizontal, linear visual analog scale indicating their level of performance (Not Satisfactory to Satisfactory) and motivation (Not Motivated to Motivated). Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. Scores ranged from 0-100 mm, with higher scores indicating motivated and satisfactory and lower scores indicating not motivated and not satisfactory. | All randomized participants who received study drug and have evaluable data for visual analog scale. | Posted | Mean | Standard Deviation | Millimeters (mm) | Approximately 2.5 hours post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
|
|
|
|
| Secondary | Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test | The SDC Test, a digit symbol substitution test that is sensitive to changes in information processing speed, provides measures of response speed and accuracy. The test was administered prior to the simulated driving sessions. The principal test score measures the number of correct responses in 120 seconds. SDC was used in this study to measure attention, visual scanning, working memory, and speed of information processing. Scores range from 0 (No correct responses). A higher score indicates greater processing speed. | All randomized participants who received study drug and have evaluable data for driving performance. | Posted | Mean | Standard Deviation | Responses | Approximately 85 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
|
|
|
|
| Secondary | Driving Performance Using the CRCDS-MiniSim - Lane Exceedance | The CRCDS-MiniSim is a PC-based research driving simulator that provides a realistic automotive driving environment. The present study employs the Country Vigilance-Divided Attention (CVDA) driving scenario, a 62.1 mile (100 km), monotonous, two lane highway driving task that includes a secondary visual vigilance task (DA). The monotonous Country Vigilance scenario has been demonstrated to be sensitive to detect the effects of fatigue or sleepiness on driving performance. Lane exceedance is the number of lane exceedances, an indication of lane position control, (i.e., the driver's ability to stay within his/her lane), as measured by the number of times that the front left or right tire of the vehicle crosses over the right or left lane boundary. | All randomized participants who received study drug and have evaluable data for driving performance. | Posted | Mean | Standard Deviation | Lane Exceedances | Approximately 90 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
|
|
|
|
| Other Pre-specified | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Data presented are the number of participants who experienced 1 or more AEs (all causalities and drug-related) and serious AEs (SAEs). A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this record. | All randomized participants who received study drug. | Posted | Count of Participants | Participants | No | Up To 35 days |
|
|
|
| Secondary | Driving Performance Using the CRCDS-MiniSim - Speed Deviation | The CRCDS-MiniSim is a PC-based research driving simulator that provides a realistic automotive driving environment. The present study employs the Country Vigilance-Divided Attention (CVDA) driving scenario, a 62.1 mile (100 km), monotonous, two lane highway driving task that includes a secondary visual vigilance task (DA). The monotonous Country Vigilance scenario has been demonstrated to be sensitive to detect the effects of fatigue or sleepiness on driving performance. Speed deviation is a measure of intra-individual variability. Measures that assess an individual's failure to maintain consistent performance are more sensitive to sedation than are measures of absolute performance. | All randomized participants who received study drug and have evaluable data for driving performance. | Posted | Mean | Standard Deviation | meter per second (m/sec) | Approximately 90 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence |
|
|
|
|
| 0 |
| 85 |
| 1 |
| 85 |
| 8 |
| 85 |
| EG001 | Lasmiditan 50mg | Participants received 50mg of Lasmiditan tablets given as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. | 0 | 87 | 0 | 87 | 34 | 87 |
| EG002 | Lasmiditan 100mg | Participants received 100mg of Lasmiditan tablets given as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. | 0 | 86 | 0 | 86 | 47 | 86 |
| EG003 | Lasmiditan 200mg | Participants received 200mg of Lasmiditan tablets given as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. | 0 | 89 | 0 | 89 | 62 | 89 |
| EG004 | Alprazolam 1mg | Participants received 1mg of Alprazolam tablets as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. | 0 | 85 | 0 | 85 | 71 | 85 |
| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
Details of the Study and its results shall not be publicized in any form without prior consent of the Sponsor. Such approval is necessary to prevent premature disclosure of trade secrets and other confidential information.
| D009422 | Nervous System Diseases |
| D006571 | Heterocyclic Compounds |
| LS Mean |
| 2.3 |
| 2-Sided |
| 95 |
| 1.8306 |
| 2.6926 |
| Superiority |
| Mixed Models Analysis | <0.0001 | LS Mean | 2.9 | 2-Sided | 95 | 2.4239 | 3.2800 | Superiority |
| Mixed Models Analysis | <0.0001 | LS Mean | 3.4 | 2-Sided | 95 | 2.9568 | 3.8193 | Superiority |
| Mixed Models Analysis | <0.0001 | LS Mean | -1.8 | 2-Sided | 95 | -2.2137 | -1.3546 | Superiority |
| Mixed Models Analysis | <0.0001 | LS Mean | -1.1 | 2-Sided | 95 | -1.5574 | -0.6956 | Superiority |
| Mixed Models Analysis | 0.0142 | LS Mean | -0.5 | 2-Sided | 95 | -0.9642 | -0.1081 | Superiority |
| VAS Self-appraisal |
|
| LS Mean |
| -24.2 |
| 2-Sided |
| 95 |
| -30.3631 |
| -18.1357 |
| Superiority |
| Mixed Models Analysis | <.0001 | LS Mean | -28.4 | 2-Sided | 95 | -34.4420 | -22.2897 | Superiority |
| Mixed Models Analysis | <0.0001 | LS Mean | -30.4 | 2-Sided | 95 | -36.5068 | -24.2770 | Superiority |
| Mixed Models Analysis | <.0001 | LS Mean | 17.8 | 2-Sided | 95 | 11.7029 | 23.8908 | Superiority |
| Mixed Models Analysis | 0.0489 | LS Mean | 6.1 | 2-Sided | 95 | 0.0297 | 12.2554 | Superiority |
| Mixed Models Analysis | 0.5123 | LS Mean | 2.0 | 2-Sided | 95 | -4.0500 | 8.1021 | Superiority |
| Mixed Models Analysis | <.0001 | LS Mean | -26.4 | 2-Sided | 95 | -32.4956 | -20.3628 | Superiority |
| Mixed Models Analysis | <.0001 | LS Mean | -37.8 | 2-Sided | 95 | -43.9270 | -31.7537 | Superiority |
| Mixed Models Analysis | <.0001 | LS Mean | -46.8 | 2-Sided | 95 | -52.8147 | -40.7268 | Superiority |
| Mixed Models Analysis | <0.0001 | LS Mean | -52.6 | 2-Sided | 95 | -58.6490 | -46.4682 | Superiority |
| Mixed Models Analysis | <.0001 | LS Mean | 26.1 | 2-Sided | 95 | 20.0635 | 32.1953 | Superiority |
| Mixed Models Analysis | <.0001 | LS Mean | 14.7 | 2-Sided | 95 | 8.6325 | 20.8040 | Superiority |
| Mixed Models Analysis | 0.0605 | LS Mean | 5.8 | 2-Sided | 95 | -0.2560 | 11.8317 | Superiority |
| LS Mean |
| -6.9 |
| 2-Sided |
| 95 |
| -8.58 |
| -5.28 |
| Superiority |
| Mixed Models Analysis | <0.001 | LS Mean | -8.9 | 2-Sided | 95 | -10.52 | -7.23 | Superiority |
| Mixed Models Analysis | <0.001 | LS Mean | -11.2 | 2-Sided | 95 | -12.81 | -9.51 | Superiority |
| Mixed Models Analysis | <0.001 | LS Mean | 6.7 | 2-Sided | 95 | 5.02 | 8.31 | Superiority |
| Mixed Models Analysis | <0.001 | LS Mean | 4.2 | 2-Sided | 95 | 2.58 | 5.88 | Superiority |
| Mixed Models Analysis | <0.007 | LS Mean | 2.3 | 2-Sided | 95 | 0.64 | 3.93 | Superiority |
| LS Mean |
| 2.018 |
| 2-Sided |
| 95 |
| 1.7981 |
| 2.2380 |
| Superiority |
| Mixed Models Analysis | <0.0001 | LS Mean | 2.572 | 2-Sided | 95 | 2.3536 | 2.7909 | Superiority |
| Mixed Models Analysis | <0.0001 | LS Mean | 2.553 | 2-Sided | 95 | 2.3331 | 2.7730 | Superiority |
| Mixed Models Analysis | <0.0001 | LS Mean | -1.114 | 2-Sided | 95 | -1.3333 | -0.8948 | Superiority |
| Mixed Models Analysis | <0.0001 | LS Mean | -0.535 | 2-Sided | 95 | -0.7549 | -0.3151 | Superiority |
| Mixed Models Analysis | 0.8629 | LS Mean | 0.019 | 2-Sided | 95 | -0.1995 | 0.2379 | Superiority |
| SAEs |
|
| LS Mean |
| 0.303 |
| 2-Sided |
| 95 |
| 0.2082 |
| 0.3985 |
| Superiority |
| Mixed Models Analysis | <.0001 | LS Mean | 0.372 | 2-Sided | 95 | 0.2770 | 0.4662 | Superiority |
| Mixed Models Analysis | <.0001 | LS Mean | 0.603 | 2-Sided | 95 | 0.5080 | 0.6983 | Superiority |
| Mixed Models Analysis | <.0001 | LS Mean | -0.423 | 2-Sided | 95 | -0.5183 | -0.3286 | Superiority |
| Mixed Models Analysis | <0.0001 | LS Mean | -0.300 | 2-Sided | 95 | -0.3949 | -0.2047 | Superiority |
| Mixed Models Analysis | <0.0001 | LS Mean | -0.232 | 2-Sided | 95 | -0.3261 | -0.1370 | Superiority |